摘要:

SUMMARYA large number of highly polymorphic microsatellite markers particularly suitable for genetic linkage analysis have recently been developed. In order to facilitate integration of the genetic maps of chromosome 11q generated using these types of markers with the physical maps of 11q currently being assembled, we have regionally assigned the Genethon markers and the 11q designated index plus other commonly used polymorphic markers to ten physical intervals of 11q. These intervals are defined by translocation breakpoints immortalized in somatic cell hybrid lines and can therefore serve as readily accessible and stable landmarks for detailed map integration and facilitate the derivation and placement of new markers and cloned contigs.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01877.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYA number of human single gene disorders are now known to result from abnormal expansion of trinucleotide repeats. Spinal muscular bulbar atrophy, myotonic dystrophy, Huntington's Disease, spinocerebellar ataxia and dentatorubral‐pallidoluysian atrophy are all caused by expansions of CAG repeats. Abnormal expansion of trinucleotide repeats has only so far been described in humans, and no mouse models exist for these diseases. In order to investigate trinucleotide repeat stability in mice, the Genbank and EMBL nucleotide databases were screened to find genes containing CAG repeats. Of the sequences selected, 32 were from mouse, and in 12 of these the repeat was in transcribed sequence and contained at least seven perfect repeats. These repeats were then analysed by PCR to evaluate the degree of variability of repeat length in the various genes. Two of the genes containing variable length CAG repeats, seven in absentia homologue 1b (Sinh1b), and choline acetyl transferase (Chat), which had not previously been mapped in the mouse genome, were mapped by linkage analysis in an interspecific backcross.Sinh1bmaps very distally on the X chromosome, andChatmaps to chromosome 1

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01878.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYA cDNA clone of the NMDAR1 (isoform E) has been used to screen both lambda and eosmid genomic libraries. A genomic phage clone was identified and sequenced and was found to contain some of the 3′ coding regions of the GRIN1 gene. This clone was used to localize the gene using fluorescentin situhybridization (FISH) to normal chromosomes, and also to a lymphoblastoid cell line containing a translocation involving chromosomes 9 and 15. FISH localized the gene to chromosome 9q34.3. The clone was used to screen a panel of genomic DNAs cut with 20 restriction enzymes. A VNTR sequence 5′ to the gene, which was polymorphic for a number of restriction enzymes, was detected. A PvuII fragment of the genomic clone was found to detect the VNTR on Southern hybridization. The polymorphic VNTR marker was mapped against chromosome 9q34 markers using linkage analysis in the CEPH families. The GRIN1 gene was linked to D9S7 with a maximum lod score of 20·09 at zero recombination fraction in males and 0·03 % recombination in fe

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01879.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYAn atypically high frequency of loss of heterozygosity at chromosome 5q22 in small adenomas from a severely affected new mutation patient with adenomatous polyposis coli was recently reported. DNA homoduplex analysis has now been used to show that the deletion in the adenomas extends to include the APC locus and that the normal allele is lost. These data also prove the maternal origin of the mutation.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01880.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY32 families informative for the segregation of Tuberous sclerosis (TSC) have been examined for genetic markers on chromosomes 9, 11, 12 and 16. In one large family there was clear evidence of linkage to markers on chromosome 16p13.3 (lodscore with D16S291 of 4·7 at θ= 0) but other families were too small to give individually convincing lodscores. Combined results for all families gave positive results with ABO/DBH on chromosome 9 (max lod 2·63) and with D16S291 on chromosome 16 (max lod 3·98) at values of theta of 0·2 in each case. Further analysis showed strong evidence for heterogeneity with approximately half the families linked to a locus TSC1 on chromosome 9 between ASS and D9S298 and half to TSC2 on chromosome 16 close to D16S291. There was no definite support for a third locus although in many families this could not be excluded. In three families the segregation pattern of TSC remains unexplained. In two of these the family apparently segregates for TSC1 but in each case a single affected individual appeared to exclude the whole of the candidate region. Preliminary analysis of clinical features did not reveal any definite differences in incidence of mental handicap between individuals in different linkage groups or with different sex of the parent of origin. The frequencies of periungual fibromas and facial angiofibromas were also similar in both linkage groups. The difficulties of detecting linkage in small families where there is locus heterogeneity are discussed. The program ZZ was found to be helpful in this res

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01881.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYLinkage analysis of discrete Mendelian traits has made a major contribution to the mapping of the human genome. However, in more complex situations, particularly Mendelian disorders showing locus heterogeneity, linkage results have sometimes been misleading. The bootstrap confidence interval provides an assessment of the goodness of fit of the data to the genetic model and the presence of heterogeneity can inflate the confidence interval indicating that the fit is poor. The loss in statistical power and the potential unreliability of linkage analyses based on small samples or subsamples of pedigree material is explored and illustrated by using simulated data and also real data on 37 families affected by the heterogeneous disorder, tuberous sclerosis.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01882.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYThe problem of detecting linkage between two loci expressed as similar phenotypes and two or more marker loci from a set of families is discussed and a solution advanced. The term amphigenic is suggested for such conditions.

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01883.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYA new nonparametric method of linkage analysis is described based on identity by descent relationships between all pairs of affected relatives within a pedigree. This approach is an extension of ESPA, which only uses information from pairs of affected siblings. The new method, called ERPA, uses the risk calculation facilities of the LINKAGE programs to obtain the necessary information in a fashion which is simple to implement and which automatically generalizes to allow for marker loci which may be multiple, non‐codominant and sex‐linked. We have investigated the relative performance of ERPA, ESPA and the lod score method on simulated data. ERPA appears to be more sensitive than ESPA for detecting linkage in pedigrees with small sibships, though both nonparametric methods are inferior to the lod score method when the true mode of transmission can be specif

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01884.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYNon‐random inheritance of the two parental haplotypes among siblings affected by certain diseases has long been used to provide evidence of the presence of disease susceptibility genes. The distribution of a powerful test, calledQ, based on haplotype concordance and discordance, is derived under the null hypothesis of random inheritance of haplotypes by affected siblings. The presence of a disease gene possibly linked to one of the haplotypes causes a change in the distribution of these haplotypes in the affected siblings. This distribution is found to be that of the sum of two independent variates contributed by the two parents in all parental types except one where both parents are heterozygous for the disease allele; which is dealt with separately. For comparison, the tables showing the powers of the test along with those of another well‐known test, the N‐test of haplotype concordance, are given. This is becauseQis a modification ofNto deal with the case when information on unaffected siblings is also avai

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01885.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0003-4800    

DOI:10.1111/j.1469-1809.1994.tb01886.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY